Highly substituted lithium amide bases can be expressed by the formula (R.sub.3 M).sub.x NLi(R.sup.1).sub.y where M=Si or C, R and R.sup.1 are alkyl, cycloalkyl and alkylene groups containing 1 to 8 carbon atoms, and x+y=2. R.sub.3 M and R.sup.1 may be combined (where M=C) to give a divalent alkylene radical, yielding a lithium cyclic alkylene amide where R and R.sup.1 taken together may contain 4 to 8 carbon atoms such as the N-lithio salts of pyrrolidine and hexamethyleneimine. Highly substituted or bulky lithium amide bases of this type are used in the preparation of pharmaceutical intermediates and in general organic synthesis.
U.S. Pat. Nos. 4,595,779 and 5,002,689 describe methods for producing highly substituted lithium amide bases in ether or mixed ether/hydrocarbon solvents using lithium metal in dispersed form and an electron carrier compound such as styrene or isoprene. U.S. Pat. No. 5,149,457 describes a method of producing highly substituted lithium amide bases in solely hydrocarbon solvent media by reacting alkyllithium compounds, such as n-butyllithium, with highly substituted amine bases, such as diisobutylamine.
While useful, these and other techniques can result in the formation of undesirable byproducts. For example, the processes described in U.S. Pat. Nos. 4,595,779 and 5,002,689 can result in the reduction products ethylbenzene and 2-methyl-2-butene of the electron carriers styrene and isoprene, respectively. The process described in U.S. Pat. No. 5,149,457 results in saturated alkanes as a byproduct, resulting from protonation of the alkyllithium compounds by the highly substituted amine bases.
The presence of these by-products in the desired product, highly substituted lithium amide base solutions, is often detrimental in subsequent applications, primarily because they can pose problems in recovery of final pure solvents from recycle streams. Additionally, the alkane by-products, such as butane, can pose environmental and safety concerns.
U.S. Pat. No. 5,420,322 describes a method for circumventing this problem of by-product impurities by directly reacting the highly substituted amine base, i.e., hexamethyldisilazane, with alkali metals above their melting points, in the absence of electron carriers. Thus the reaction temperature for lithium metal is 225.degree. C. and the reactor must be made of steel (molten lithium metal attacks glass) to withstand the pressures required for use with most ordinary solvents, e.g., tetrahydrofuran and cyclohexane. The use of molten lithium metal at these reaction temperatures is hazardous, since inadvertent exposure to the ambient atmosphere would result in instant conflagration. In addition, the process is expensive with respect to energy expended and capital cost of the pressure equipment needed. Also, best results were obtained using an excess of the base, i.e., hexamethyldisilazane, thus necessitating the use of a second solvent to dissolve the reaction product after reaction was cooled to ambient temperature.